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Purpose To evaluate the characteristics of low suspicion lesions (BI-RADS 0) at blinded and non-blinded double reading of screening mammograms and to determine the potential effect of arbitration of discrepant BI-RADS 0 recalls by a third reader on screening outcome. Methods We included a series of 84,927 consecutive digital screening mammograms, double read in a blinded (43,184 screens) or non-blinded (41,743 screens) fashion, between July 2009 and July 2011. Discrepant readings were routinely recalled for further evaluation. During 2 years of follow-up, radiology, surgical and pathology reports were collected of all recalled women. Arbitration of discrepant BI-RADS 0 recalls (only one radiologist assigning a BI-RADS 0 score) was retrospectively performed by a third screening radiologist. Results At blinded and non-blinded double reading, 32.0% and 32.5% of recalls were assigned BI-RADS 0 with a positive predictive value (PPV) of 7.2% and 6.8%, respectively. Compared to non-blinded double reading, BI-RADS 0 recalls at blinded double reading showed a higher discrepancy rate (9.0 versus 4.3 per 1000 screens, p < 0.001) and false positive recall rate (10.1 versus 8.4 per 1000 screens, p = 0.012). Arbitration of discrepant BI-RADS 0 recalls would have significantly lowered recall rate (from 3.4% to 2.8% at blinded double reading, p < 0.001, and from 2.8% to 2.5% at non-blinded double reading, p = 0.008), without a decrease in cancer detection rate (from 7.5‰ to 7.3‰, p = 0.751, and from 6.6‰ to 6.5‰, p = 0.832, respectively) and program sensitivity (from 83.2% to 81.2%, p = 0.453, and from 76.0% to 74.6%, p = 0.667, respectively). Arbitration would have significantly increased the PPV at blinded double reading (from 22.3% to 26.3%, p = 0.015). Conclusion We advise arbitration of discrepant BI-RADS 0 recalls, at (non-)blinded double reading of screening mammograms, to reduce recall rates and improve the PPV of recall at blinded double reading. [ABSTRACT FROM AUTHOR]

Background Axillary reverse mapping (ARM) is a technique to map and preserve upper extremity lymphatic drainage during axillary lymph node dissection (ALND) in breast cancer patients. We prospectively evaluated the metastatic involvement of ARM-nodes in patients who underwent an ALND for clinically node positive disease following (neo)adjuvant chemotherapy (NAC) in comparison to patients in whom primary ALND was performed without NAC. Patients and methods Patients with clinically node positive invasive breast cancer, confirmed by fine needle aspiration cytology and scheduled for primary ALND were enrolled in the study. Patients were separated into two groups: one group treated with NAC (NAC+ group) and one group not treated with NAC (NAC− group). ARM was performed in all patients by injecting blue dye into the ipsilateral upper extremity. During ALND, ARM-nodes were first identified and removed separately, followed by a standard ALND. Results 91 patients were included in the NAC+ and 21 patients in the NAC− group. There was no difference in the ARM visualization rate between the two groups (86.8% for NAC+ group versus 90.5% for NAC− group, P = 0.647). In the NAC+ group 16.5% of the patients had metastatic involvement of the ARM-nodes versus 36.8% of the patients in the NAC− group ( P = 0.048). Conclusion The risk of metastatic involvement of ARM-nodes in clinically node positive breast cancer patients is significantly lower in patients who have received NAC. [ABSTRACT FROM AUTHOR]

Abstract: Background: To examine variation in time and place in axillary staging and treatment of patients with ductal carcinoma in situ (DCIS) of the breast. Methods: Trends in patients with DCIS recorded in the Eindhoven Cancer Registry diagnosed in 1991–2010 (n = 2449) were examined. Results: The use of breast conserving surgery (BCS) went from 17% to 67% in 1991–2010 and administration of radiotherapy after BCS increased to 89%. Axillary lymph node dissection decreased to almost 0%, while sentinel node biopsy was performed in 65% of patients in 2010. The proportion who underwent BCS varied between hospitals from 49% to 80%; the proportion without axillary staging ranged from 21% to 60%. Patients with screen-detected DCIS were more likely to receive BCS. Conclusion: There was considerable variation in the use of BCS, radiotherapy, and axillary staging of DCIS over time and between hospitals. Patients with DCIS were more likely to be treated with BCS if their disease was detected by screening. [Copyright &y& Elsevier]

Abstract: Background: The purpose of the study was to determine the effectiveness of routine follow-up to detect contralateral breast cancer (CBC) in young women. Methods: We used the data of the population-based Eindhoven Cancer Registry, which covers the southern part of the Netherlands. Between 1988 and 2005, 1451 women aged ≤40 years were treated for early-stage breast cancer with breast-conserving treatment or mastectomy. Results: Of the 94 patients who developed CBC 17 had an in situ carcinoma. Fifty-seven CBCs (61%) were diagnosed more than 5 years after the primary tumour. Forty-two CBCs (45%) were detected during routine follow-up visits, while 52 (55%) presented between two visits. Of the CBC diagnosed between two visits, only 27 (60%) were visible on mammography. Of the invasive CBCs more than 25% was larger than 2 cm in diameter and in 34% positive axillary lymph nodes were found. Conclusions: These figures indicate that routine follow-up does not guarantee early detection of CBC in young women with breast cancer. [Copyright &y& Elsevier]

Abstract: Background: Few studies have focussed on the prognosis of young women with local recurrence (LR) after breast-conserving therapy and the factors that can be used to predict their prognosis. Methods: We studied the outcome and related prognostic factors in 124 patients with an isolated local recurrence in the breast following breast-conserving surgery and radiotherapy for early stage breast cancer diagnosed at the age of 40 years or younger. Results: The median follow-up of the patients after diagnosis of LR was 7.0 years. At 10 years from the date of salvage treatment, the overall survival rate was 73% (95% CI, 63–83), the distant recurrence-free survival rate was 61% (95% CI, 53–73), and the local control rate (i.e. survival without subsequent LR or local progression) was 95% (95% CI, 91–99). In the multivariate analysis, the risk of distant metastases also tended to be higher for patients with LR occurring within 5 years after BCT, as compared to patients with LR more than 5 years after BCT (Hazard ratio [HR], 1.89; p = 0.09). A worse distant recurrence-free survival was also observed for patients with a LR measuring more than 2 cm in diameter, compared to those with a LR of 2 cm or smaller (HR, 2.88; p = 0.007), and for patients with a LR causing symptoms or suspicious findings at clinical breast examination, compared to those with a LR detected by breast imaging only (HR 3.70; p = 0.03). Conclusions: These results suggest that early detection of LR after BCT in young women can improve treatment outcome. [Copyright &y& Elsevier]

Abstract: Background: Internationally, there is no consensus on the pathology protocol to be used to examine the sentinel lymph node (SN) in breast cancer patients. Previously, we reported that ultra-staging led to more axillary lymph node dissections (ALND). The question was, whether ultra-staging is effective in reducing the risk of regional relapse. Methods: From January 2002 to July 2003, 541 patients from 4 hospitals were prospectively registered when they underwent a SN biopsy. In hospitals A, B, and C, 3 levels of the SN were examined pathologically, whereas in hospital D at least 7 additional levels were examined. Patients with a positive SN, including isolated tumor cells, underwent an ALND. This analysis focuses on the 341 patients with a negative SN. Primary endpoint was 5-year regional recurrence rate. Results: In hospital D 34% of the patients had a negative SN as compared to 71% in hospitals A, B, and C combined (p < 0.001). At 5 years follow-up, 9 (2.6%) patients had developed a regional lymph node relapse. In hospital D none of the patients had a regional recurrence, as compared to 9 (2.9%) cases of recurrence in hospitals A, B, and C. Conclusion: The less intensified SN pathology protocol appeared to be associated with a slightly increased risk of regional recurrence. The absolute risk was still less than 3%, and does not seem to justify the intensified SN pathology protocol of hospital D. [Copyright &y& Elsevier]

Abstract: Background: To assess the feasibility of lymphatic mapping and determine the lymphatic drainage pathways in patients previously treated with breast conserving therapy (BCT). Methods: We included patients without current breast cancer that previously received BCT with sentinel node biopsy (SNB) and/or axillary lymph node dissection (ALND) for primary breast cancer. The study population consisted of 44 patients and was divided into two groups according to previous surgical treatment of the axilla: 22 patients after previous SNB and 22 patients after previous ALND. Standard lymphatic mapping was performed and the lymphatic drainage pattern was registered. Drainage located outside the ipsilateral axilla was recorded as aberrant. Results: Lymphoscintigraphy revealed a drainage pattern in 17 of 44 patients (39%). The identification rate in the SNB-group was 41% and 36% in the ALND-group (P =0.760). 8 patients (18%) showed aberrant drainage, which tended to be more frequent in the ALND-group than in the SNB-group (27% versus 9%, P =0.122). Lymphatic drainage to the contralateral axilla was observed in 2 patients, both previously treated with ALND. Conclusions: Lymphatic mapping seems feasible after previous BCT with axillary treatment, in spite of a relatively low identification rate. Aberrant drainage tends to be more frequent after previous treatment with ALND. [Copyright &y& Elsevier]

Abstract: Background: Axillary reverse mapping (ARM) is a technique that discerns axillary lymphatic drainage of the arm from the breast. This study was performed to evaluate both the feasibility of this technique and the proportion of metastatic involvement of ARM-nodes. Patients and methods: Patients with invasive breast cancer and an indication for axillary lymph node dissection (ALND) were enrolled in the study: patients with a tumor-positive sentinel lymph node (SLN+-group) and patients who had axillary metastases proven by preoperative cytology (CP-N+-group) were distinguished. ARM was performed in all patients by injecting blue dye. During surgery ARM-nodes were identified and removed first, followed by ALND. Results: Between October 2009 and June 2011 93 patients underwent ARM. There were 43 patients in the SLN+-group and 50 patients in the CP-N+-group. No significant differences in visualization rate of ARM-nodes between the groups (86 vs 94% respectively, P = 0.196) were identified. In the SLN+-group none of the ARM-nodes contained metastases versus 11 patients (22%) in the CP-N+-group (P = 0.001). Patients receiving neoadjuvant systemic therapy had a significantly lower risk of additional axillary lymph node metastases (24.6 vs 44.4%, P = 0.046). Discussion: The ARM procedure is technically feasible with a high visualization rate. The proportion of patients with metastases in the ARM-nodes was significantly higher in patients with proven axillary metastases than in patients with a positive SLN. Patients with SLN metastases appear to be good candidates for the ARM technique and possibly also patients with proven axillary metastases receiving neoadjuvant chemotherapy. [Copyright &y& Elsevier]

Abstract: Aim: A lack of consistency in the definition of breast cancer related lymphoedema (BCRL) and of uniform measurement criteria contribute to the wide prevalence range found in current literature. This report aims to describe the long-term prevalence of BCRL and secondly, to compare the long-term prevalence of BCRL when assessed by two objective measures and one subjective measure. Methods: The upper-limbs of 145 post-surgical breast cancer patients were evaluated for the presence of lymphoedema using the water displacement method. Two circumference methods and patient perceived swelling were applied secondarily for comparison. Limb measurements were performed once, more than five years after surgery. Results: The long-term prevalence of BCRL using water displacement was 8%. Prevalence varied when the sum of arm circumference (SOAC), the arm circumference and the self-report methods were used: 16, 31 and 17% [P < 0.001], respectively. Of the women identified with BCRL using the water displacement technique, 82% were detected with the SOAC method, 82% with the arm circumference method and 91% by self-report. Using water displacement as the gold standard the methods with the highest specificities were the SOAC (90%) and self-report method (89%), arm circumference resulted in a low specificity of 73%. Conclusion: The prevalence of BCRL more than five years after surgical treatment differs depending on the measuring method used. Our data underlines the necessity for consensus on the diagnostic criteria for BCRL. [Copyright &y& Elsevier]

Abstract: Aims: Though most studies on surgical resection of the breast tumor in patients with primary distant metastatic breast cancer (MBC) indicated that surgery is associated with prolonged overall survival, some state that this effect has been confounded by indication and timing of surgery. In this study we analyzed these possible confounders and their relation to overall survival. Methods: To determine the impact of potential confounders, individual charts of 279 patients with primary MBC were reviewed. Results: The median survival in patients treated with surgery of the breast tumor was 39 months, compared to 15 months for those without surgery (p < 0.0001). The median survival of patients with symptomatic metastatic disease (n = 112) was 19 months, compared to 22 months for those without symptomatic disease (n = 167) (p = 0.15). Patients who received surgery and whose metastases were detected before surgery of the breast tumor had taken place (n = 40) had a median survival of 38 months, compared to 40 months for patients in whom the metastatic disease was diagnosed after surgery (n = 43) (p = 0.81). Conclusion: Presence of symptomatic metastatic disease was no significant prognostic factor for patients with distant metastasis at diagnosis, neither was the timing of surgery. It is unlikely that the prolonged survival after surgery is explained by these potentials confounders. [Copyright &y& Elsevier]

Abstract: Gastric cancer is one of the main causes of cancer-related deaths around the world. The prevalence of early gastric cancer (EGC) among all gastric cancers of 45–51% in Japan, but only 7–28% in Western countries. The prevalence of EGC is growing partly because of better diagnostics and screening programmes. Possible treatment options for EGC treatment are expanded by the introduction of endoscopic mucosal resection and endoscopic submucosal dissection Therefore, detailed knowledge about nodal metastatic risk is warranted. We performed a systematic review of the literature concerning studies investigating the role of sentinel lymph node biopsy in EGCr and whether there is enough proof to introduce SLN as a part of treatment for EGC in the Netherlands. Several detection substances (dye or radiocolloid) and injection methods (submucosal or subserosal) are investigated. An overall sensitivity percentage of 85.4% was found. In comparison, high and clinically sufficient percentages were observed for specificity (98.2%), negative predictive value (90.7%) and accuracy (94%). Subgroup analyses showed that the combination of dye and radiocolloid detection substances is the best method for sentinel lymph node detection in early gastric cancer. However, the precise method of sentinel lymph node biopsy in EGC has to be determined further. Large, randomized series should be initiated in Europe to address this issue. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate axillary staging and management in patients with local recurrence (LR) after a previous negative sentinel lymph node biopsy (SNB). Methods: Between 1999 and 2008, 130 patients with previous negative SNB developed a LR of breast or chest wall. After examination of clinical records, 70 patients met the inclusion criteria and remained available for analysis. Results: Thirty-seven patients were treated with axillary lymph node dissection (ALND), followed by axillary radiotherapy in 9 cases. In 26 of these 37 patients no positive axillary lymph nodes were found. Nineteen patients received no treatment of the axilla at all. Of those, 9 were older than 70 years of age at diagnosis of LR. In 13 patients a second SNB was attempted, but was successful in only 5 cases. Eight patients underwent a complementary ALND. Overall, positive lymph nodes were detected in 13 of the 50 patients who underwent axillary staging, either by SNB or ALND. The median length of follow-up of the 70 patients following their diagnosis of LR was 24 months (range 2–81 months). During this follow-up period one patient developed an axillary recurrence. This was a patient who refused to undergo ALND but was given locoregional radiotherapy instead. Conclusions: In the absence of guidelines for staging and management of the axilla at time of LR of breast or chest wall, many different strategies are being used. Considering the high rate of positive axillary lymph nodes in these patients, repeat surgical staging is appropriate. [Copyright &y& Elsevier]

Abstract: Objective: Recent studies indicate that removal of the primary tumour may have a beneficial effect on mortality risk of patients with primary distant metastatic breast cancer (stage IV), although most of them did not rule out confounding by the presence of co-morbidity. In this retrospective study the impact of surgical resection of the primary tumour on the survival of patients with primary distant metastatic disease is investigated, taking into account the presence of co-morbidity and other potential confounders. Methods: Between 1993 and 2004, 15 769 patients with breast cancer were diagnosed in the south of the Netherlands. This study included the 728 patients with distant metastatic disease at initial presentation, which was 5% of all patients. Of them, 40% had surgery of the primary tumour. Follow-up was carried out until 1 July 2006. Results: Median survival of the patients who had surgery of their primary tumour was significantly longer than for the patients who did not have surgery (31 vs. 14 months). The 5-year survival rates were 24.5% and 13.1%, respectively (p <0.0001). In a multivariable Cox regression analysis, adjusting for age, period of diagnosis, T-classification, number of metastatic sites, co-morbidity, use of loco-regional radiotherapy and use of systemic therapy, surgery appeared to be an independent prognostic factor for overall survival (HR=0.62; 95% CI 0.51–0.76). Conclusion: Removal of the primary tumour in patients with primary distant metastatic disease was associated with a reduction of the mortality risk of around 40%. The association was independent of age, presence of co-morbidity and other potential confounders, but a randomized controlled trial will be needed to rule out residual confounding. [Copyright &y& Elsevier]

Although the internal mammary (IM) lymph node status is a major prognostic factor in breast cancer, IM nodal staging is not common practice. In order to improve nodal staging, we have routinely performed IM sentinel node (SN) biopsy and have adjusted adjuvant treatment accordingly. We reviewed the outcome of these patients. Data from 764 patients were available for follow-up. A total of 406 patients had no lymph node metastases (group 1), 330 patients had axillary metastases (group 2), 7 patients had IM metastases only (group 3) and 21 patients had both axillary and IM metastases (group 4). Mean follow-up was 46 months. Prognosis did not appear to be worse for patients with IM metastases compared to those with axillary metastases only, which might indicate that they benefit from improved staging and tailored adjuvant treatment algorithms. However, long-term follow-up data, preferably in larger series, are needed to support our findings. [Copyright &y& Elsevier]

Abstract: Introduction: Nowadays, axillary sentinel node (SN) biopsy is a standard procedure in the staging of breast cancer. Although the internal mammary (IM) lymph node status is a major independent prognostic factor in breast cancer patients, sampling of IM sentinel nodes (IMSNs) is not performed routinely. The aim of this study was to determine the likelihood of finding IM lymph node metastases in case of IM hotspots on lymphoscintigraphy and evaluate the relevance of IMSN biopsy as a method to improve staging. Patients and methods: Between April 1997 and May 2006, a total of 1008 consecutive patients with clinically node-negative operable primary breast cancer were enrolled in a prospective study on SN biopsy. Both axillary and IMSNs were sampled, based on lymphoscintigraphy, intraoperative gamma probe detection and blue dye mapping, using 10mCi (370MBq) 99mTc-nanocolloid injected peritumorally, and 0.5–1.0ml Patent Blue V injected intradermally. Results: Lymphoscintigraphy showed axillary sentinel nodes in 98% (989/1008) and IMSNs in 20% of the patients (196/1008). Sampling the IM basin, as based on the results of lymphoscintigraphy, was successful in 71% of the patients (139/196) and revealed metastases in 22% (31/139). In 29% of the patients with positive IMSNs (9/31) no axillary metastases were found. Conclusion: Evaluation of IMSNs improves nodal staging in breast cancer. Patients with IM hotspots on lymphoscintigraphy have a substantial risk (22%) of metastatic involvement of the IM chain. In addition, true IM node-negative patients can be spared the morbidity associated with adjuvant radiotherapy. [Copyright &y& Elsevier]

Summary: The use of Breast Conserving Surgery (BCS) followed by radiotherapy (BSC-RT) in pT1 (⩽2cm) and pT2-tumours (2–⩽5cm) was investigated in the Netherlands from 1990 to 2001. From the Netherlands Cancer Registry, patients were selected with invasive tumours <5.0cm. Trends were determined and explanatory factors were determined by multivariate logistic regression. Over the period 52,937 pT1-tumours and 36,285 pT2-tumours were diagnosed. The percentage BCS and BCS-RT in patients 80 years or older remained lowest. Multivariate logistic regression revealed that older age (70+), tumour size >2cm, positive clinical nodes and medium hospital size decreased the chance of BCS. For BCS-RT the same factors and negative pathological nodes decreased the chance of BCS-RT. Between regions large differences were seen. Cancer registry data are useful to monitor the guideline implementation strategies. Multidisciplinary treatment planning, surgeon and patient education could increase the use of BCS combined with RT in all age groups. [Copyright &y& Elsevier]

Abstract: Aim: Sentinel lymph node biopsy (SLNB) without completion axillary lymph node dissection (ALND) is replacing ALND as the axillary staging procedure of choice in breast cancer patients with a clinically negative axilla even though it is unclear whether this influences patient survival. Our aim was to compare the survival of breast cancer patients with a negative SLNB without completion ALND to that of extensive ALND-negative patients. Methods: Eindhoven Cancer Registry data on breast cancer patients diagnosed between 1989 and 2002 with follow-up to 1 January 2005 was used. Survival was compared between 880 SLNB-negative women (median follow-up 3.6years) without completion ALND and 1681 ALND-negative women (median follow-up 7.7years) with at least 10 axillary nodes removed. Conclusions were made after correcting for age, tumour size, tumour location, tumour histology, tumour grade, mitotic activity index (MAI), hormone receptor status, and local and systemic treatment in uni- and multivariate analyses. Results: Crude 5-year survival rates were 85% for ALND-negative and 89% for SLNB-negative breast cancer patients (p =0.026). After correction for potential confounders in a multivariate Cox regression analyses, the hazard ratio for overall mortality of ALND-negative compared to SLNB-negative patients without completion ALND was 1.23 (95% confidence interval: 0.93–1.64). Conclusion: Survival after a SLNB without completion ALND is at least equivalent to after an extensive ALND in node-negative breast cancer patients. This means that the SLNB only can safely replace ALND as the procedure of choice for axillary staging in breast cancer patients with a clinically negative axilla. [Copyright &y& Elsevier]

Abstract: Aims: The aim of this study was to identify a subgroup of patients with breast cancer that can safely avoid axillary dissection. Methods: Using data collected by the Eindhoven Cancer Registry, we compared the clinico-pathological features of 489 patients with only one positive lymph node to those of 817 patients with more than one positive lymph node in the axilla. All patients underwent complete axillary dissection, not preceded by a sentinel node biopsy. Results: Tumour size greater than 1cm, harvesting more than 15 axillary lymph nodes at histopathological examination, metastasis size larger than 2mm, extranodal extension, and nodal involvement of the axillary apex are independently associated with the occurrence of more than one metastatic axillary lymph node. Conclusion: No subgroup could be identified in which axillary dissection can always be omitted. However, tumour size<1cm, finding a micrometastasis rather than a macrometastasis, and especially not finding extranodal extension were independently associated with finding only one positive axillary lymph node. [Copyright &y& Elsevier]

Objectives: To determine the extent and characteristics of delay in breast cancer diagnosis in women recalled at screening mammography.Methods: We included a consecutive series of 817,656 screens of women who received biennial screening mammography in a Dutch breast cancer screening region between 1997 and 2016. During at least 3.5 years follow-up, radiological reports and biopsy reports were collected of all recalled women. The inclusion period was divided into four cohorts of four years each. We determined the number of screen-detected cancers and their characteristics, and assessed the proportion of recalled women who experienced a diagnostic delay of at least 4 months in breast cancer confirmation.Results: The proportion of recalled women who experienced diagnostic delay decreased from 7.5 % in 1997-2001 (47/623) to 3.0 % in 2012-2016 (67/2223, P < 0.001). The proportion of women with a delay of at least two years increased from 27.7 % (13/47) in 1997-2001 to 75.7 % (53/70) in 2012-2016 (P < 0.001). Cancers with a diagnostic delay > 2 years were more frequently invasive (P = 0.009) than cancers with a diagnostic delay of 4-24 months. The most frequent cause of diagnostic delays was incorrect radiological classifications by clinical radiologists (55.2 % overall) after recall.Conclusions: The proportion of recalled women with a delayed breast cancer diagnosis has more than halved during two decades of screening mammography. Delays in breast cancer diagnosis are characterized by longer delay intervals, although the proportion of these delays among all screen-detected cancers has not increased. Preventing longer delays in breast cancer confirmation may help improve breast cancer survival. [ABSTRACT FROM AUTHOR]